The purpose of this study is the determination of the three dimensional structure of proton translocating ATPases. Single crystal X-ray diffraction and electron microscopy techniques are used for the structure determination of the F1-ATPase from rat liver mitochondria. The study is being carried out in two stages. The first stage, which is partially completed, involves the calculation and interpretation of electron density maps at 9 angstrom resolution. The second stage is planned to a resolution of 3.5 angstrom, the maximum resolution that can be obtained from the present crystals. Binding of nucleotides, inhibitors and effectors will be studied using difference Fourier techniques. Attempts are also being made to obtain crystalline materials from other preparations of proton translocating ATPases and their fragments.